ALPHA-ADRENERGIC RECEPTOR BINDING

现在清楚的是，有一个大家族的不同受体， 去甲肾上腺素（NE）和肾上腺素（EPI）。最少7公斤 不同的肾上腺素能受体亚型（β 1-，β 2-，β 3-，α 1a-， alpha 1b-，alpha 2a-，alpha 2b-）已经被鉴定。 然而，关于这些亚型的重要性的信息很少 对发射器的响应。因为它们通常在细胞上共存， 在相同的第二信使系统上的主要行动， 发射器通常将由多个发射器上的组合动作来确定。 亚型 我们的主要假设是NE和EPI通过以下途径产生作用： 同时激活许多不同的受体亚型，这些 亚型以复杂的方式相互作用，以确定 cell.我们建议使用一天大鼠脑的原代培养物， 描述第二信使对个体亚型的反应，阐明 它们的相互作用，并确定细胞如何响应发射器 是被控制的 将处理以下具体目标： 1.为了确定第二信使的受体亚型， 对NE和EPI的反应。烷化剂和竞争性拮抗剂将 用于隔离对单个亚型的反应。 2.为了确定特定亚型的同时共激活是否具有 抑制、累加、增强或冗余效应 其他亚型。 3.为了确定慢性激动剂暴露是否会下调每个 亚型独立，以及对NE和EPI的反应是否增加或 降低 4.为了开始确定是否每个肾上腺素能受体亚型激活 不同的信号转导机制，通过检查的影响， 对不同亚型的反应进行各种操作。 在下一个项目期间，我们希望澄清职能作用， 不同肾上腺素能受体亚型的相互作用。

It is now clear that there is a large family of different receptors for norepinephrine (NE) and epinephrine (EPI). At least 7 pharmacologically distinct adrenergic receptor subtypes (beta l-, beta 2-, beta3-, alpha 1a-, alpha1b-, alpha2a-, alpha2b-) have already been identified. However,little information is available on the importance of these subtypes in responses to transmitters. Since they often coexist on cells and have primary actions on the same second messenger systems, the net response to transmitter will often be determined by combined actions on multiple subtypes. Our major hypothesis is that NE and EPI cause their effects through simultaneous activation of many different receptor subtypes, and that these subtypes interact in complex ways to determine the net response of the cell. We propose to use primary cultures from one day old rat brain to characterize second messenger responses to individual subtypes, clarify their interactions, and determine how the cellular response to transmitter is controlled. The following specific aims will be addressed: 1. To determine the receptor subtypes involved in second messenger responses to NE and EPI. Alkylating agents and competitive antagonists will be used to isolate responses to individual subtypes. 2. To determine if simultaneous co-activation of particular subtypes have inhibitory, additive, potentiative or redundant effects on responses to other subtypes. 3. To determine whether chronic agonist exposure down-regulates each subtype independently, and whether responses to NE and EPI are increased or decreased. 4. To begin to determine whether each adrenergic receptor subtype activates a different signal transduction mechanism by examining the effect of various manipulations on responses to different subtypes. During the next project period we hope to clarify the functional roles and interactions of the different adrenergic receptor subtypes.